The skin, which covers the surface of the human body, is the largest organ of the human body. The skin protects the human body, responds to sensation, and regulates the human body temperature. The structure of the skin, from most superficial to least superficial, includes the epidermis, dermis, and hypodermis. In general, skin aging increases with age. There are two classifications of factors that cause skin aging: endogenous and exogenous. Endogenous aging is a natural aging process of the human body. The following are just some of the ways endogenous aging may affect the skin. The keratinocyte stem cells decrease along with increase in age which may cause the disorders of cells in the basal layer and the decrease of hyaluronic acid and moisturizing factors. In addition, the decrease of hormone (such as sebaceous glands) secretion may slow the metabolism of the skin, and thus, leads to a loss of tension and elasticity of the skin. The deterioration of the functions of fibroblasts in the dermis may also slowly decrease the production of collagen and elastin, thus, causes the connective tissue in the dermis to degenerate, leading to flaccidity and even wrinkling of the skin. The degeneration of connective tissues in the dermis may decrease the water storage function of the skin, leading to skin dryness and water deficiency. Lastly, the atrophy of epidermis and dermis may decrease the protective ability of the skin, or lead to a loss of elasticity of the blood vessels and result in subcutaneous hemorrhages.
Exogenous aging is caused by the direct contact between the skin and the environment, in which the skin is exposed to extrinsic factors, such as sunshine, pollution, free radicals, and smoking. Exogenous aging of the skin includes the inhibition of cellular renewal and repair, decrease in protective ability, and the accumulation of melanin. The main factor that causes skin aging is damage caused by ultraviolet (UV) rays from the sun, which may accelerate skin aging by 5 to 10 times. Long wavelength UV (UVA) and medium wavelength UV (UVB) are the most common UV rays in daily life. Long-term exposure to UVB may stimulate fibroblasts in the dermis to express collagenases to degrade collagen, thus, leads to a decrease of collagen density, a denaturation of collagen, and a loss of elasticity of the skin. In addition, the melanocytes will start to degenerate, leading to uneven color in the skin. As a result, free radicals are overly generated in the skin, leading to the formation of skin darkness and dark spots, and even various cutaneous carcinomas.
To date, there are many methods for preventing and repairing skin aging, including extracellular matrix (ECM) supplement therapy, Clostridium botulinum injection, and exfoliative physiotherapy. The ECM supplement therapy includes applying collagen, elastin, hyaluronic acid or vitamin E onto the surface of the skin. However, the structure of these molecules is too big to be absorbed effectively by the skin and get into the dermis layer. The therapeutical effect of ECM supplement therapy is limited because these molecules cannot be maintained in the human body for over 9 months. Though Clostridium botulinum injection can improve skin flaccidity, its effect can only be maintained for 3 to 6 months and it may cause side effects, such as upper eyelid ptosis, rigid and strange facial expression, or muscle weakness at the injected region. Though exfoliative physiotherapy can remove aged horniness and stimulate skin proliferation, there are many side effects, including weakened skin, slow repair and many postoperative complications.
Cellular therapy is another option for treating skin aging, which comprises the use of stem cells to improve the damaged skin tissue. For example, an adipose-derived stem cell (ADSC) is a multipotent stem cell separated from fat tissue, similar to an umbilical cord stem cell, and is one kind of human mesenchymal stem cell. ADSCs are highly plastic and can be classified into various histocytes, such as neural cells, vascular endothelial cells, cardiocytes, hepatocytes, chondrocytes, and myocytes. Formerly, most of the fat tissue obtained from liposuction surgery was thrown away as waste. However, researches have found that fat tissue is rich in mesenchymal stem cells, which have the potential of external proliferation and multiple differentiations, and thus can be used in the renewal and repair of tissues and organs. These cells can be acquired with low invasiveness and with less harm to the human body. In addition, these cells can be cultured in vitro and can be widely used in various types of body tissues. These cells can move to the wounded regions spontaneously and repair the wounds.
Currently, cellular therapy must be conducted by injecting the cells into a subject. The most common way to inject a certain amount of stem cells is subcutaneously. However, this therapy is invasive and carries some risks, and will cause many traumatic wounds that may affect the appearance of the skin. Furthermore, the application of such a traditional cellular therapy has many limitations because living cells are used in this therapy, the safety of the living cells should be evaluated strictly before injection, and when applied to humans, the living cells should originate from human stem cells.
In view of the limited efficacy and side effects of the above ECM supplement therapy and Clostridium botulinum injection and the potential risks and limitations of the cellular therapy, there is still a need for an effective and simple method for repairing skin aging.
The present invention provides an extract extracted from mesenchymal stem cells for resolving the above issues. The mesenchymal stem cell extract can be applied topically and get into the human body, to promote the expression of hyaluronic acid, elastin, collagen and/or reticulin in the skin, stimulate cell proliferation at the administered region, stimulate cells at the administered region to secrete a trophic factor, and stimulate endogenous hematopoietic progenitor cells (HPC) to gather and proliferate at the administered region. The mesenchymal stem cell extract can be used in combination with a heating means to provide an excellent effect of repairing skin aging.